JP2002502815A - 抗菌剤 - Google Patents
抗菌剤Info
- Publication number
- JP2002502815A JP2002502815A JP2000530203A JP2000530203A JP2002502815A JP 2002502815 A JP2002502815 A JP 2002502815A JP 2000530203 A JP2000530203 A JP 2000530203A JP 2000530203 A JP2000530203 A JP 2000530203A JP 2002502815 A JP2002502815 A JP 2002502815A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- compound
- group
- hydrogen
- amino
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Withdrawn
Links
- 239000003242 anti bacterial agent Substances 0.000 title description 18
- -1 hydroxy, mercapto Chemical class 0.000 claims abstract description 330
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 123
- 239000001257 hydrogen Substances 0.000 claims abstract description 119
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 95
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 75
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 66
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 49
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 29
- 125000003118 aryl group Chemical group 0.000 claims abstract description 28
- 125000005843 halogen group Chemical group 0.000 claims abstract description 28
- 239000004599 antimicrobial Substances 0.000 claims abstract description 24
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 24
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 20
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 20
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 16
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims abstract description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 14
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 13
- 125000001246 bromo group Chemical group Br* 0.000 claims abstract description 13
- 125000001309 chloro group Chemical group Cl* 0.000 claims abstract description 13
- 125000001153 fluoro group Chemical group F* 0.000 claims abstract description 13
- 125000002346 iodo group Chemical group I* 0.000 claims abstract description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 13
- 125000004450 alkenylene group Chemical group 0.000 claims abstract description 3
- 150000001875 compounds Chemical class 0.000 claims description 227
- 239000000203 mixture Substances 0.000 claims description 66
- 238000000034 method Methods 0.000 claims description 65
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 51
- 150000002431 hydrogen Chemical class 0.000 claims description 46
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
- 125000004432 carbon atom Chemical group C* 0.000 claims description 36
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 36
- 229910052757 nitrogen Inorganic materials 0.000 claims description 31
- 230000001580 bacterial effect Effects 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 235000008206 alpha-amino acids Nutrition 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 23
- 125000003342 alkenyl group Chemical group 0.000 claims description 22
- 230000000845 anti-microbial effect Effects 0.000 claims description 22
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 20
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 20
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 19
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 19
- 238000012360 testing method Methods 0.000 claims description 18
- 125000004429 atom Chemical group 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000003277 amino group Chemical group 0.000 claims description 15
- 230000000694 effects Effects 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 15
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 15
- 150000001371 alpha-amino acids Chemical class 0.000 claims description 14
- 229910052799 carbon Inorganic materials 0.000 claims description 13
- 230000000844 anti-bacterial effect Effects 0.000 claims description 12
- 125000002837 carbocyclic group Chemical group 0.000 claims description 12
- 238000011109 contamination Methods 0.000 claims description 12
- 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 12
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 11
- 238000000338 in vitro Methods 0.000 claims description 11
- 239000003112 inhibitor Substances 0.000 claims description 11
- 125000000304 alkynyl group Chemical group 0.000 claims description 10
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 10
- 208000015181 infectious disease Diseases 0.000 claims description 10
- 125000001424 substituent group Chemical group 0.000 claims description 10
- 125000002252 acyl group Chemical group 0.000 claims description 9
- 235000001014 amino acid Nutrition 0.000 claims description 9
- 150000001413 amino acids Chemical class 0.000 claims description 9
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 9
- 125000000524 functional group Chemical group 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 9
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 9
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 7
- 102000004190 Enzymes Human genes 0.000 claims description 7
- 108090000790 Enzymes Proteins 0.000 claims description 7
- 125000004122 cyclic group Chemical group 0.000 claims description 7
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 7
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 7
- 125000006239 protecting group Chemical group 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 6
- 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 claims description 6
- 208000035143 Bacterial infection Diseases 0.000 claims description 6
- 208000022362 bacterial infectious disease Diseases 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- 239000003795 chemical substances by application Substances 0.000 claims description 6
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000005010 perfluoroalkyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000547 substituted alkyl group Chemical group 0.000 claims description 6
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 5
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 5
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 5
- 238000012216 screening Methods 0.000 claims description 5
- 125000000069 2-butynyl group Chemical group [H]C([H])([H])C#CC([H])([H])* 0.000 claims description 4
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
- 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims description 4
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 229910052717 sulfur Inorganic materials 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000005862 (C1-C6)alkanoyl group Chemical group 0.000 claims description 3
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 3
- 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
- QOXOZONBQWIKDA-UHFFFAOYSA-N 3-hydroxypropyl Chemical group [CH2]CCO QOXOZONBQWIKDA-UHFFFAOYSA-N 0.000 claims description 3
- 125000003143 4-hydroxybenzyl group Chemical group [H]C([*])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 claims description 3
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 claims description 3
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 3
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical group CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 3
- 125000003047 N-acetyl group Chemical group 0.000 claims description 3
- 125000005073 adamantyl group Chemical group C12(CC3CC(CC(C1)C3)C2)* 0.000 claims description 3
- 125000000958 aryl methylene group Chemical group 0.000 claims description 3
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 3
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 230000001747 exhibiting effect Effects 0.000 claims description 3
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 3
- 125000002950 monocyclic group Chemical group 0.000 claims description 3
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 125000004923 naphthylmethyl group Chemical group C1(=CC=CC2=CC=CC=C12)C* 0.000 claims description 3
- 229910052760 oxygen Inorganic materials 0.000 claims description 3
- 125000003884 phenylalkyl group Chemical group 0.000 claims description 3
- 125000004344 phenylpropyl group Chemical group 0.000 claims description 3
- PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims description 3
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 2
- 108700040121 Protein Methyltransferases Proteins 0.000 claims description 2
- 102000055027 Protein Methyltransferases Human genes 0.000 claims description 2
- 125000004419 alkynylene group Chemical group 0.000 claims description 2
- 238000005574 benzylation reaction Methods 0.000 claims description 2
- 239000003610 charcoal Substances 0.000 claims description 2
- 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 230000011987 methylation Effects 0.000 claims description 2
- 238000007069 methylation reaction Methods 0.000 claims description 2
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 2
- 238000006467 substitution reaction Methods 0.000 claims description 2
- 241001504505 Troglodytes troglodytes Species 0.000 claims 1
- 150000001336 alkenes Chemical class 0.000 claims 1
- 150000002500 ions Chemical class 0.000 description 179
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 123
- 238000005160 1H NMR spectroscopy Methods 0.000 description 80
- 239000011734 sodium Substances 0.000 description 65
- 108010026809 Peptide deformylase Proteins 0.000 description 43
- 239000000243 solution Substances 0.000 description 43
- 102100021418 Peptide deformylase, mitochondrial Human genes 0.000 description 40
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 39
- 230000002829 reductive effect Effects 0.000 description 37
- 239000012230 colorless oil Substances 0.000 description 33
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 32
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 26
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 24
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 24
- 239000012267 brine Substances 0.000 description 23
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 23
- 239000003921 oil Substances 0.000 description 22
- 235000019198 oils Nutrition 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- 238000006243 chemical reaction Methods 0.000 description 20
- 239000007787 solid Substances 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 108090000623 proteins and genes Proteins 0.000 description 19
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- MSTNYGQPCMXVAQ-RYUDHWBXSA-N (6S)-5,6,7,8-tetrahydrofolic acid Chemical compound C([C@H]1CNC=2N=C(NC(=O)C=2N1)N)NC1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 MSTNYGQPCMXVAQ-RYUDHWBXSA-N 0.000 description 17
- 241000894006 Bacteria Species 0.000 description 17
- 150000001408 amides Chemical class 0.000 description 17
- 229940088710 antibiotic agent Drugs 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- 102000004169 proteins and genes Human genes 0.000 description 17
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- 239000005460 tetrahydrofolate Substances 0.000 description 16
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- 210000004027 cell Anatomy 0.000 description 15
- 239000000706 filtrate Substances 0.000 description 15
- 235000018102 proteins Nutrition 0.000 description 15
- 238000005481 NMR spectroscopy Methods 0.000 description 13
- 239000012074 organic phase Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- 229910052786 argon Inorganic materials 0.000 description 12
- 239000006260 foam Substances 0.000 description 12
- 229910000029 sodium carbonate Inorganic materials 0.000 description 12
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 11
- 239000003814 drug Substances 0.000 description 11
- 235000019441 ethanol Nutrition 0.000 description 11
- XJLATMLVMSFZBN-VYDXJSESSA-N actinonin Chemical compound CCCCC[C@H](CC(=O)NO)C(=O)N[C@@H](C(C)C)C(=O)N1CCC[C@H]1CO XJLATMLVMSFZBN-VYDXJSESSA-N 0.000 description 10
- 238000003818 flash chromatography Methods 0.000 description 10
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 9
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 9
- XJLATMLVMSFZBN-UHFFFAOYSA-N actinonine Natural products CCCCCC(CC(=O)NO)C(=O)NC(C(C)C)C(=O)N1CCCC1CO XJLATMLVMSFZBN-UHFFFAOYSA-N 0.000 description 9
- 239000003054 catalyst Substances 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- KDGKTJGPFXIBEB-UHFFFAOYSA-N n-hydroxyformamide Chemical class ONC=O KDGKTJGPFXIBEB-UHFFFAOYSA-N 0.000 description 9
- 238000000746 purification Methods 0.000 description 9
- 239000000741 silica gel Substances 0.000 description 9
- 229910002027 silica gel Inorganic materials 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- IQFYYKKMVGJFEH-XLPZGREQSA-N Thymidine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](O)C1 IQFYYKKMVGJFEH-XLPZGREQSA-N 0.000 description 8
- 230000005764 inhibitory process Effects 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 239000000758 substrate Substances 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 7
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 7
- 229940024606 amino acid Drugs 0.000 description 7
- 239000008346 aqueous phase Substances 0.000 description 7
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 7
- 239000002953 phosphate buffered saline Substances 0.000 description 7
- 238000002360 preparation method Methods 0.000 description 7
- 239000003981 vehicle Substances 0.000 description 7
- WQLVEAXQSUHALO-ZCFIWIBFSA-N (2s)-2-amino-n,n,3,3-tetramethylbutanamide Chemical compound CN(C)C(=O)[C@@H](N)C(C)(C)C WQLVEAXQSUHALO-ZCFIWIBFSA-N 0.000 description 6
- 102000007590 Calpain Human genes 0.000 description 6
- 108010032088 Calpain Proteins 0.000 description 6
- 241000588724 Escherichia coli Species 0.000 description 6
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 108010059993 Vancomycin Proteins 0.000 description 6
- 239000002253 acid Substances 0.000 description 6
- 229940125782 compound 2 Drugs 0.000 description 6
- 239000002609 medium Substances 0.000 description 6
- 238000004809 thin layer chromatography Methods 0.000 description 6
- 229960003165 vancomycin Drugs 0.000 description 6
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 6
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 6
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- DVEIDGKSJOJJJU-UHFFFAOYSA-N benzotriazole-1-carbaldehyde Chemical compound C1=CC=C2N(C=O)N=NC2=C1 DVEIDGKSJOJJJU-UHFFFAOYSA-N 0.000 description 5
- 229940041514 candida albicans extract Drugs 0.000 description 5
- 150000001728 carbonyl compounds Chemical class 0.000 description 5
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/06—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to hydrogen atoms or to acyclic carbon atoms
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GBGB9806300.1A GB9806300D0 (en) | 1998-03-24 | 1998-03-24 | Antibacterial agents |
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GBGB9810463.1A GB9810463D0 (en) | 1998-05-16 | 1998-05-16 | Antibacterial agents |
GB9828318.7 | 1998-12-22 | ||
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PCT/GB1999/000386 WO1999039704A1 (en) | 1998-02-07 | 1999-02-05 | Antibacterial agents |
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JP2006501155A (ja) * | 2002-05-31 | 2006-01-12 | スミスクライン・ビーチャム・コーポレイション | ペプチドデホルミラーゼ阻害剤 |
JP2006522054A (ja) * | 2003-04-02 | 2006-09-28 | ノバルティス アクチエンゲゼルシャフト | 結晶性n−ホルミルヒドロキシルアミン化合物 |
JP2009513485A (ja) * | 2003-06-26 | 2009-04-02 | ノバルティス アクチエンゲゼルシャフト | ある種の抗菌性n−ホルミルヒドロキシルアミン化合物の製造に有用な中間体の製造法 |
JP2011516399A (ja) * | 2007-06-07 | 2011-05-26 | イルドン ファーマシューティカル カンパニー リミテッド | 新規ぺプチドデホルミラーゼ阻害化合物とその製造方法 |
JP2012502974A (ja) * | 2008-09-19 | 2012-02-02 | ファイザー・インク | 抗菌剤として有用なヒドロキサム酸誘導体 |
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ES2221359T3 (es) * | 1998-02-07 | 2004-12-16 | Vernalis (Oxford) Ltd | Agentes antibacterianos. |
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CA2393825A1 (en) * | 1999-12-17 | 2001-06-21 | Versicor, Inc. | Novel succinate compounds, compositions and methods of use and preparation |
AR028075A1 (es) * | 2000-05-05 | 2003-04-23 | Smithkline Beecham Corp | Inhibidores de la peptido-desformilasa |
AR029916A1 (es) * | 2000-05-05 | 2003-07-23 | Smithkline Beecham Corp | N-formil-n-hidroxi-ariloxi alquilaminas y metodos para tratar infecciones bacterianas |
AU2002230385A1 (en) * | 2000-09-25 | 2002-04-15 | Questcor Pharmaceuticals, Inc. | Peptide deformylase inhibitors |
EP1339400B1 (en) | 2000-11-23 | 2005-06-29 | Vernalis (Oxford) Ltd | N-formyl hydroxylamine derivatives as inhibitors of bacterial polypeptide deformylase for treating microbial infections |
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JP4220377B2 (ja) * | 2001-04-05 | 2009-02-04 | スミスクライン・ビーチャム・コーポレイション | ペプチドデホルミラーゼ阻害物質 |
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DE60219630T2 (de) | 2001-06-15 | 2007-12-27 | Vicuron Pharmaceuticals, Inc., Fremont | Bicyclische pyrrolidinverbindungen |
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GB0128943D0 (en) * | 2001-12-04 | 2002-01-23 | Novo Pharmaceuticals De Ltd | Bacterial enzyme inhibitors |
GB0208579D0 (en) * | 2002-04-13 | 2002-05-22 | British Biotech Pharm | Antibacterial agents |
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AU2004216178B2 (en) * | 2003-02-21 | 2008-07-03 | Novartis Ag | Chemical process for the preparation of intermediates to obtain N-formyl hydroxylamine compounds |
KR100527361B1 (ko) * | 2003-04-01 | 2005-11-09 | 주식회사 프로메디텍 | 데포르밀라제 저해제, 이의 제조방법, 및 이를 포함하는조성물 |
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1999
- 1999-02-05 ES ES99904977T patent/ES2221359T3/es not_active Expired - Lifetime
- 1999-02-05 KR KR1020007008492A patent/KR100600518B1/ko not_active IP Right Cessation
- 1999-02-05 GB GB0016855A patent/GB2349884A/en not_active Withdrawn
- 1999-02-05 WO PCT/GB1999/000386 patent/WO1999039704A1/en not_active Application Discontinuation
- 1999-02-05 BR BR9907689-6A patent/BR9907689A/pt not_active Application Discontinuation
- 1999-02-05 JP JP2000530203A patent/JP2002502815A/ja not_active Withdrawn
- 1999-02-05 PT PT99904977T patent/PT1052984E/pt unknown
- 1999-02-05 US US09/355,489 patent/US6423690B1/en not_active Expired - Fee Related
- 1999-02-05 PL PL99342296A patent/PL194240B1/pl unknown
- 1999-02-05 TR TR2000/02311T patent/TR200002311T2/xx unknown
- 1999-02-05 CA CA002320476A patent/CA2320476A1/en not_active Abandoned
- 1999-02-05 DK DK99904977T patent/DK1052984T3/da active
- 1999-02-05 DE DE69917221T patent/DE69917221T2/de not_active Expired - Fee Related
- 1999-02-05 EP EP99904977A patent/EP1052984B1/en not_active Expired - Lifetime
- 1999-02-05 NZ NZ505675A patent/NZ505675A/xx unknown
- 1999-02-05 HU HU0102901A patent/HUP0102901A3/hu unknown
- 1999-02-05 IL IL13731299A patent/IL137312A/xx active IP Right Grant
- 1999-02-05 AT AT99904977T patent/ATE266394T1/de not_active IP Right Cessation
- 1999-02-05 CN CN99802752A patent/CN1298299A/zh active Pending
- 1999-02-05 AU AU25292/99A patent/AU749699B2/en not_active Ceased
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2000
- 2000-08-04 NO NO20003969A patent/NO20003969L/no not_active Application Discontinuation
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2002
- 2002-04-30 US US10/134,754 patent/US6787522B2/en not_active Expired - Fee Related
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2004
- 2004-07-29 US US10/901,065 patent/US7148198B2/en not_active Expired - Fee Related
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Cited By (6)
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JP2006501155A (ja) * | 2002-05-31 | 2006-01-12 | スミスクライン・ビーチャム・コーポレイション | ペプチドデホルミラーゼ阻害剤 |
JP2006522054A (ja) * | 2003-04-02 | 2006-09-28 | ノバルティス アクチエンゲゼルシャフト | 結晶性n−ホルミルヒドロキシルアミン化合物 |
JP2009513485A (ja) * | 2003-06-26 | 2009-04-02 | ノバルティス アクチエンゲゼルシャフト | ある種の抗菌性n−ホルミルヒドロキシルアミン化合物の製造に有用な中間体の製造法 |
JP2011516399A (ja) * | 2007-06-07 | 2011-05-26 | イルドン ファーマシューティカル カンパニー リミテッド | 新規ぺプチドデホルミラーゼ阻害化合物とその製造方法 |
JP2012502974A (ja) * | 2008-09-19 | 2012-02-02 | ファイザー・インク | 抗菌剤として有用なヒドロキサム酸誘導体 |
US9340493B2 (en) | 2008-09-19 | 2016-05-17 | Pfizer Inc. | Hydroxamic acid derivatives useful as antibacterial agents |
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